Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma
Evaluate safety, feasibility, persistence, and anti-tumor effect of infused haploidentical donor-derived natural killer (NK) cells and low-dose interleukin-2 (IL-2).
- Quantification of cytokine levels;
- Assessment of NK cell immunophenotype and function.
|Neuroblastoma||Drug: Fludarabine Drug: Cyclophosphamide Biological: Natural Killer Cell Infusion Drug: Mesna Drug: Interleukin-2||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Study to Infuse Haploidentical Natural Killer Cells in Patients With Relapsed or Refractory Neuroblastoma|
- Participant Disease Response [ Time Frame: 1 Year for overall patient response, or until disease progression ]Neuroblastoma International Response Criteria: Complete Response (CR): No evidence of disease (primary and metastasis) clinically & radiographic studies, (homovanillic acid (HVA)/vanillylmandelic acid (VMA) normal). Very Good Partial Response (VGPR): >90% reduction in primary tumor, resolution all metastatic tumor except bone. No new bone lesions and improvement on scan of all pre-existing lesions; HVA/VMA decreased >90%. Partial Response (PR): 50-90% reduction primary and all measurable metastatic lesions, 0-1 bone marrow samples with tumor; scans of bone lesions same as VGPR. HVA/VMA decreased 50-90%. Mixed Response (MR): > 50% reduction any measurable disease (primary or metastases); no new lesions; <25% increase in any existing lesion (exclude bone marrow evaluation). No Response (NR): No new lesions; < 25% increase in existing lesion. Progressive Disease (PD): Any new lesions. Increase <25% in measurable lesion, previous negative bone marrow positive for tumor.
- Number of Participants Infused Haploidentical Donor-derived Natural Killer (NK) Cells and Low-dose Interleukin-2 (IL-2) [ Time Frame: 21 days, up to 1 year ]Feasibility of an infused allogeneic donor NK cell product and IL-2 following a cyclophosphamide and fludarabine preparative regimen to treat relapsed neuroblastoma after autologous peripheral blood stem cell (PBSC) transplant where feasibility is defined as being able to infuse NK cells on day 0.
|Study Start Date:||June 2008|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Fludarabine + Cyclophosphamide + NK Cell Infusion
Fludarabine 25 mg/m^2 intravenous (IV) Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2. Cyclophosphamide 60 mg/kg IV Daily Over 2 Hours On Days -5 and -4. Natural Killer Cell Infusion on Day 0. Mesna 12 mg/kg By Vein, Over about 15 minutes, 5 Times Per Day on Days -5 and -4. Interleukin-2 subcutaneously three times weekly for 9 total doses following NK Cell Infusion.
25 mg/m^2 By Vein Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2.
Other Names:Drug: Cyclophosphamide
60 mg/kg By Vein Daily Over 2 Hours On Days -5 and -4
Other Names:Biological: Natural Killer Cell Infusion
Natural Killer Cell Infusion on Day 0.
Other Names:Drug: Mesna
12 mg/kg By Vein, Over about 15 minutes, Five Times Per Day on Days -5 and -4.
Other Name: MesnexDrug: Interleukin-2
Received under skin three times weekly for 9 total doses following NK Cell Infusion:
For patients weighing 45 kg or more, dose administered is 10 Million units three times weekly for 9 total doses. For patients less than 45 kg, dose administered is 5 Million units/m2 (max dose 10 Million units) three times weekly for 9 total doses.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00698009
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Susan S. Kelly, MD||M.D. Anderson Cancer Center|